Serotonergic and non-serotonergic projections from the interpeduncular nucleus to the ventral hippocampus in the rat

doi:10.1016/0304-3940(84)90256-8

Neuroscience Letters

Volume 51, Issue 1, 28 September 1984, Pages 19-24

https://doi.org/10.1016/0304-3940(84)90256-8 Get rights and content

Abstract

The localization of serotonin and non-serotonin-containing cell bodies in the interpeduncular nucleus of the rat that project to the hippocampal formation was studied using the technique of retrograde tracing of Granular Blue and immunohistochemistry on the same sections. The results indicate that the caudal magnocellular subnucleus (pars dorsalis magnocellularis) and, to a lesser extent, the caudal part of the lateral subnucleus (pars lateralis) of the interpeduncular nucleus send serotonin as well as non-serotonin fibers to the ventral hippocampus.

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Retrograde demonstration of hippocampal afferents from the interpeduncular and reuniens nuclei
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H.J. Groenewegen et al.
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Identification of serotonin and non-serotonin-containing neurons of the mid-brain raphe projecting to the entorhinal area and the hippocampal formation
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Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals
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Cited by (29)

Temporary inactivation of interpeduncular nucleus impairs long but not short term plasticity in the perforant-path dentate gyrus synapses in rats
2020, Behavioural Brain Research
Citation Excerpt :
However, the ways that these projections terminate to either the DG granular cells or GABAergic interneurons through the excitatory/inhibitory projections still remains to be investigated. On the other hand, IPN could act on the hippocampus through several structures which are involved in the hippocampal dependent learning and memory processes and theta rhythm activity including raphe nuclei, nucleus incertus, septum and supra mammillary nucleus [21,23,24,38,39]. In Fig. 10, we proposed a diagrammatic reconstruction of these direct and indirect pathways from IPN to the hippocampus.
The interconnectivity of the hippocampus, interpeduncular nucleus (IPN) and several brain structures which are involved in modulating hippocampal theta rhythm activity makes a complicated dynamic network of interconnected regions and highlights the role of IPN in the hippocampal dependent learning and memory. In the present study we aimed to address whether IPN is involved in the perforant path-dentate gyrus (PPDG) short term and long term synaptic plasticity in rats. To silent IPN transiently, lidocaine was injected through the implanted cannula above the IPN. To evaluate short term plasticity, paired pulses stimulation of PPDG synapses were used upon IPN temporary inactivation. Furthermore, long term plasticity was investigated by measuring the induction and maintenance of PPDG synapses long term potentiation (LTP) after high frequency stimulation (HFS) of the mentioned pathway following to IPN inactivation. The results showed that IPN reversible inactivation had no effect on short term plasticity of PPDG synapses. However, IPN inactivation before the PPDG high frequency stimulation could significantly suppress both the population spike (PS) and fEPSP-LTP induction compared to the saline group. Conversely, IPN inactivation had no significant effect on maintenance of both PS-LTP and fEPSP-LTP. All together our study suggests the contribution of IPN in the PPDG synaptic plasticity and excitability of DG granule cells which could be through direct and/or indirect pathways from IPN to the hippocampus.
Reversible inactivation of interpeduncular nucleus impairs memory consolidation and retrieval but not learning in rats: A behavioral and molecular study
2018, Behavioural Brain Research
Citation Excerpt :
Therefore, the use of lidocaine in the present study allowed us to reversibly silence any connection between IPN and hippocampus, without considering its neurochemical signature. Previously the existence of direct anatomical connections mainly between the dorsocaudal part of the IPN and the ventral hippocampus has been reported [13,26,51]. But the neurochemical signature of these connections is not well understood yet.
The Interpedundular nucleus (IPN) is a small midbrain structure located deeply between the two cerebral peduncles. The strategic placement of this nucleus makes it a possible relay between structures involved in the modulation of hippocampal theta rhythm activity. In this study we aimed to investigate how reversible inactivation of IPN could affect the acquisition, consolidation and retrieval phases of memory in passive avoidance (PA) and Morris water maze (MWM) tasks. To support our data, molecular studies were performed in order to detect possible changes in the expression of proteins related to learning and memory in the hippocampus. To address this issue rats’ IPN was reversibly inactivated by microinjection of lidocaine hydrochloride (4%). After the behavioral studies, the phosphorylation of CREB and P70, and c-fos expression levels in the hippocampus were determined using western blotting and immunohistochemistry respectively. Our results in the PA and MWM tasks showed that IPN reversible inactivation could impair immediate post training consolidation and retrieval while it had no effect on the acquisition phase. In addition, there was a deficit in the retention of the MWM working memory. Our data showed the ratio of pCREB/CREB, pP70/P70 and c-fos expression in the hippocampus significantly decreased after IPN reversible inactivation. Collectively, the results show that behaviorally defined changes could be due to what happens molecularly in the hippocampus after IPN reversible inactivation. It is concluded that IPN not only makes part of a network involved in the modulation of hippocampal theta rhythm activity, but also is actively engaged in hippocampal memory formation.
Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatory systems
2014, Cell Reports
Citation Excerpt :
Because there was slight nonspecific labeling in serotonergic nuclei adjacent to injection sites, we excluded data from these areas for the following analysis. IPN is located just anterior to MR, and the caudal apical and caudal ventrolateral subnuclei of IPN (IPA and IPVL/IPL; Hale and Lowry, 2011) contain some serotonin neurons (Groenewegen and Steinbusch, 1984). IPA and IPL contained a small number of starter neurons but other IPN subnuclei did not.
Serotonin and dopamine are major neuromodulators. Here, we used a modified rabies virus to identify monosynaptic inputs to serotonin neurons in the dorsal and median raphe (DR and MR). We found that inputs to DR and MR serotonin neurons are spatially shifted in the forebrain, and MR serotonin neurons receive inputs from more medial structures. Then, we compared these data with inputs to dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). We found that DR serotonin neurons receive inputs from a remarkably similar set of areas as VTA dopamine neurons apart from the striatum, which preferentially targets dopamine neurons. Our results suggest three major input streams: a medial stream regulates MR serotonin neurons, an intermediate stream regulates DR serotonin and VTA dopamine neurons, and a lateral stream regulates SNc dopamine neurons. These results provide fundamental organizational principles of afferent control for serotonin and dopamine.
Possible glutamatergic/aspartatergic projections to the supramammillary nucleus and their origins in the rat studied by selective [<sup>3</sup>H]D-aspartate labelling and immunocytochemistry
2002, Neuroscience
The supramammillary neurons projecting directly to the hippocampus or indirectly via the septum participate in the regulation of hippocampal theta activity. Inputs to the supramammillary nucleus are only partly specified neurochemically. Glutamate appears to be an excitatory transmitter in this cell group, however, the origin of the glutamatergic afferents is unknown. The present investigations were devoted to study this question. The transmitter-selective [³H]D-aspartate retrograde transport method was used injecting the tracer into the lateral subregion of the nucleus. The radioactive tracer was visualized by autoradiography. Non-selective retrograde tracing experiments were also performed for reference injecting wheat germ agglutinin-conjugated colloidal gold into the same supramammillary region. Retrogradely radiolabelled neurons in various numbers were detected in several brain regions including medial septum–diagonal band complex, lateral septum, rostral part of medial and lateral preoptic areas, lateral habenula, ventral premammillary nucleus, apical subregion of interpeduncular nucleus, laterodorsal tegmental nucleus, and dorsal and median raphe nuclei. Radiolabelled neurons in the mentioned raphe nuclei were serotonin-immunonegative. In the non-selective retrograde tracing experiments combined with immunocytochemistry, about 50% of the retrogradely labelled neurons in the raphe nuclei was serotonin-immunonegative, showing that not only serotonergic raphe neurons project to the supramammillary nucleus.
The findings indicate that a significant part of the afferents from telencephalic, diencephalic and brainstem regions to the supramammillary nucleus may contain glutamate/aspartate as neurotransmitter. The most important functional implications of these observations concern the role of the supramammillary nucleus in controlling the electrical activity of the hippocampus, and in particular the generation and maintenance of the theta rhythm.
The fasciculus retroflexus controls the integrity of REM sleep by supporting the generation of hippocampal theta rhythm and rapid eye movements in rats
1998, Brain Research Bulletin
The fasciculus retroflexus (FR) fiber bundle comprises the intense cholinergic projection from the medial division of the habenula nucleus (Hbn) of the epithalamus to the interpeduncular nucleus (IPN) of the limbic midbrain. Due to the widespread connections of the Hbn and IPN, it could be surmised that the FR is integrated in the processings of various subsystems that are known to be involved in the sleep–wake mechanisms; relevant sites include the limbic forebrain and midbrain areas and more caudal pontine structures. Consequently, the present study addressed the significance of the FR in the spontaneous sleep–wake stage-associated variations of the different activity patterns of frontal cortex and hippocampal electroencephalograms (EEGs), the electrooculogram, and body movements, in freely behaving rats that had been subjected to either bilateral electrolytic lesioning of the FR or control operations. The evolution of different state combinations was assessed by the combinatory analysis of different activity stages appearing on the 6-h records. As compared to the control-operated group, the FR lesioning substantially reduced the time spent in rapid eye movement (REM) sleep by 79%, moderately decreased the duration of the intermediate state of sleep by 29%, and quiet waking state by 44%, but had virtually no effects on the durations of different types of non-REM sleep (i.e., drowsiness that which involved quiet sleep or slow-wave sleep containing delta and spindle state components) or on the times of active waking behavior that corresponded to the body movements. Quantitative decomposition analyses revealed marked variations in the frontal cortex and hippocampal activity as well as REM during the course of the extracted sleep–wake stages described and there were also some group differences. Of those individual features that were used to determine different sleep–wake stages, the overall hippocampal theta time (41% decrease) and single REM frequency (71% reduction during the REM sleep) were most affected. In contrast, the various properties of desynchronization/synchronization patterns of frontal cortex EEGs were consistently hardly influenced by the FR lesioning. Therefore, the present data suggest the involvement of the FR in the REM sleep processes by establishing prominent associations with the limbic and REM control mechanisms that involve the hippocampus and plausibly pontine ocular activity networks.
Habenulo-interpeduncular descending pathways and their relationship to enkephalin- and somatostatin-immunoreactive neurons in the interpeduncular nucleus of human fetuses
1993, Neuroscience
The interpeduncular nucleus of six human fetuses aged 15 (one specimen), 26 (one specimen), 38 (one specimen) and 40 (three specimens) gestation weeks was studied by immunohistochemistry for enkephalin and somatostatin localization and immunohistochemistry coupled with silver staining. Enkephalin-positive and somatostatin-positive cells were detected, the former initially at 15 weeks gestation and the latter at 26 weeks gestation. They appeared to receive long afferents from the habenular region and projected short efferents to adjacent cells devoid of enkephalin and somatostatin positivity.
We postulate that these enkephalin- and somatostatin-positive neurons function as modulatory interneurons in the habenulo-interpeduncular and related pathways.

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Neuroscience Letters

Abstract

References (17)

Retrograde demonstration of hippocampal afferents from the interpeduncular and reuniens nuclei

Neurosci. Lett.

Efferent connections of the dorsal tegmental region in the rat, studied by means of anterograde transport of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L)

Brain Res.

Identification of serotonin and non-serotonin-containing neurons of the mid-brain raphe projecting to the entorhinal area and the hippocampal formation

A combined immunohistochemical and fluorescent tracing study in the rat brain

Neuroscience

Distribution of 5-hydroxytryptamine-containing neuronal perikarya in the rat interpeduncular nucleus

Neurosci. Lett.

Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals

Neuroscience

A study of the subcortical afferents of the hippocampal formation in the rat

Neuroscience

Fluorescent antibody methods

Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in cell bodies of brain stem neurons

Acta physiol. scand.

Cited by (29)

Temporary inactivation of interpeduncular nucleus impairs long but not short term plasticity in the perforant-path dentate gyrus synapses in rats

Reversible inactivation of interpeduncular nucleus impairs memory consolidation and retrieval but not learning in rats: A behavioral and molecular study

Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatory systems

Possible glutamatergic/aspartatergic projections to the supramammillary nucleus and their origins in the rat studied by selective [<sup>3</sup>H]D-aspartate labelling and immunocytochemistry

The fasciculus retroflexus controls the integrity of REM sleep by supporting the generation of hippocampal theta rhythm and rapid eye movements in rats

Habenulo-interpeduncular descending pathways and their relationship to enkephalin- and somatostatin-immunoreactive neurons in the interpeduncular nucleus of human fetuses